Tohoku J. Exp. Med., 2013 November, 231(3)

Reduced Expression of Prostacyclin Synthase and Nitric Oxide Synthase in Subcutaneous Arteries of Type 2 Diabetic Patients

SITI SAFIAH MOKHTAR,¹ PAUL M. VANHOUTTE,² SUSAN W.S. LEUNG,² MOHD IMRAN YUSOF,³ WAN AZMAN WAN SULAIMAN,⁴ ARMAN ZAHARIL MAT SAAD,⁴ RAPEAH SUPPIAN⁵ and AIDA HANUM GHULAM RASOOL¹

¹Pharmacology Vascular Laboratory, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia
²Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
³Department of Orthopaedic, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia
⁴Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia
⁵School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia

Diabetic endothelial dysfunction is characterized by impaired endothelium-dependent relaxation. In this study, we measured the expression of endothelial nitric oxide synthase (eNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin synthase (PGIS), and prostacyclin receptor (IP) in subcutaneous arteries of type-2 diabetic and non-diabetic patients. Subcutaneous arteries were dissected from tissues from seven diabetics (4 males and 3 females) and seven non-diabetics (5 males and 2 females) aged between 18 to 65 years, who underwent lower limb surgical procedures. Diabetics had higher fasting blood glucose compared to non-diabetics, but there were no differences in blood pressure, body mass index and age. Patients were excluded if they had uncontrolled hypertension, previous myocardial infarction, coronary heart disease, renal or hepatic failure and tumor. The relative expression levels of eNOS, COX-1, COX-2, PGIS and IP receptor were determined by Western blotting analysis, normalized with the β-actin level. Increased expression of COX-2 was observed in subcutaneous arteries of diabetics compared to non-diabetics, whereas the expression levels of eNOS and PGIS were significantly lower in diabetics. There were no significant differences in expression levels of COX-1 and IP receptor between the two groups. Immunohistochemical study of subcutaneous arteries showed that the intensities of eNOS and PGIS staining were lower in diabetics, with higher COX-2 staining. In conclusion, type-2 diabetes is associated with higher COX-2 expression, but lower eNOS and PGIS expression in subcutaneous arteries. These alterations may lead to impaired endothelium-dependent vasodilatation, and thus these proteins may be potential targets for protection against the microvascular complications of diabetes.

keywords —— diabetes; endothelial dysfunction; microcirculation; nitric oxide synthase; prostacyclin synthase

© 2013 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2013, 231, 217-222

Correspondence: Aida Hanum Ghulam Rasool, Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu 16150, Malaysia.

e-mail: aida@kb.usm.my